The mechanism for the renal vasoconstriction induced by acetylocholine (ACh) in idomethacin (Indo)-treated dogs was examined in dogs receiving an infusion of either verapamil (V) or dibutyryl cyclic AMP (db-AMP). Renal arterial infusion of V (60 ug/min) attenuated, but did not eliminate, the fall in renal plasma flow induced by ACh (40 ug/min) in Indo-treated dogs (5 mg/kg). Renin secretory rate, however, did not show a rise. Renal arterial infusion of db-cAMP (6 mg/min) restored the natriuretic and vasodilatory effects of ACh in Indo-treated dogs. The data suggest that ACh causes an increase in intracellular CA++ concentration by stimulating Ca++ influx and the release of Ca++ from intracellular storage sites in Indo-treated dogs. The increase in cytosolic Ca++ concentration then leads to contraction of vascular smooth muscle resulting in renal vasoconstriction.